The overall goal of this study, in response to (PAR-97-074) "Innovative approaches to developing new technologies", is to develop the potential of a small scale computed tomography (CT) for cross-sectional imaging of small rodent models. The laboratory mouse and rat are key participants in medical research in areas including carcinogenesis, pharmaceutical development, cardiovascular disease, AIDS research, device testing, and so on. The resolution of commercial CT scanners for human imaging is on the order of 500 mum, and this resolution is too poor to properly image the anatomy of a mouse or a rat, due to the small physical dimensions of these animals. Consequently, to study changes in these research animals, it often is necessary to sacrifice them and perform direct anatomical visualization (e.g. thick section microscopy). In many studies, cohorts of animals are subjected to some research regiment, and then at various time points, some fraction of the cohort is sacrificed and their anatomies are studied post mortem. The long term objective of this technology-development proposal is to develop a CT scanner specifically designed to produce high resolution (e.g. 50 to 100 mum pixels) cross-sectional images of suitably restrained and anethesized small rodents, in vivo. The specific aims are to: (1) design and build the CT hardware, (2) design, write and test the necessary software to control the rotation and data acquisition, (3) using theoretical and computer simulation methods, develop and optimize a CT reconstruction algorithm tailored to the specific geometry of the small scanner, and finally (4) to measure the imaging performance of the CT scanner. Synchrotron sources have much greater fluence rates than x-ray fluoroscopic systems, however they are not widely available and are too expensive to be practical for this purpose. The proposed system will make use of x-rays from a general purpose fluoroscopic system, and will be specifically designed to adapt easily to most fluoroscopic x-ray tubes, which are widely available in any medical center. A micro-CT system is currently operational in the PI's laboratory, which employs 50 mum pixels and has a limiting spatial resolution of 10 cycles per mm. This system produces excellent images of high contrast objects such as the structure of bone, however is it fundamentally limited in its ability to image soft tissue structure within an animal due to signal to noise limitation. The SNR limitations are imposed by the limited x- ray output of the fluoroscopic x-ray system used. In this proposal, we hope to extend the performance of micro-CT systems by building a system which is capable of using the much higher x-ray fluence rates which exist closer to the x-ray focal spot. For example, by moving the detector from its current location 51 cm from the source to 10 cm away, the x-ray fluence rate can be increased 26 fold (inverse square law), improving the theoretical SNR by a factor of 5 (SNR approximately DOSE 1/2). However, by moving the detector so close to the x-ray source, it's physical size becomes a major detriment to achieving spatial resolution. Techniques are proposed (multi-step deconvolution) to compensate for this "focal spot blurring" in the image reconstruction process. The focus of this proposal is to study various CT scanner designs with specific attention to producing a practical solution to imaging small animals; as such a system will have the potential for broad impact on biomedical research. Furthermore, with the ability to study anatomical changes within a single animal, the proposed scanner will make it possible for researchers to substantially reduce the number of animals used and simultaneously achieve higher statistical power, since the bio-structure of individuals can be monitored serially over time, the variation in response between individuals to the treatment under study is eliminated.